OCT angiography calculation with optimized signal processing

ABSTRACT

Methods and systems for angiographic imaging with optical coherence tomography (OCT) are described using ratio-based and angiographic deviation based calculations. In using these calculations to determine motion, arbitrary interframe permutations may be used, post- calculated, non-linear results for projection visualization may be averaged, poor matches may be eliminated on an A-line by A-line basis, windowing functions may be used to improve results, partial spectrums may be used when capturing data, and a minimum intensity threshold may be used for determining which pixels to use.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. application Ser. No.15/964,871, filed on Apr. 27, 2018, entitled “OCT ANGIOGRAPHYCALCULATION WITH OPTIMIZED SIGNAL PROCESSING”, which claims priority toU.S. application Ser. No. 15/091,288, filed on Apr. 5, 2016, entitled“OCT ANGIOGRAPHY CALCULATION WITH OPTIMIZED SIGNAL PROCESSING”, whichissued as U.S. Pat. No. 9,984,459 on May 29, 2018, and which claimspriority to: (1) U.S. Provisional Application Ser. No. 62/147,911, filedon Apr. 15, 2015, entitled “OCT ANGIOGRAPHY USING A RATIO-BASEDCALCULATION WITH OPTIMIZED SIGNAL PROCESSING”; (2) U.S. ProvisionalApplication Ser. No. 62/171,533, filed on Jun. 5, 2015, entitled “OCTANGIOGRAPHY USING A RATIO-BASED CALCULATION WITH OPTIMIZED SIGNALPROCESSING”; (3) U.S. Provisional Application Ser. No. 62/222,767, filedon Sep. 23, 2015, entitled “OCT ANGIOGRAPHY USING A RATIO-BASEDCALCULATION WITH OPTIMIZED SIGNAL PROCESSING”; and (4) U.S. ProvisionalApplication Ser. No. 62/263,389, filed on Dec. 4, 2015, entitled “OCTANGIOGRAPHY USING A RATIO-BASED CALCULATION WITH OPTIMIZED SIGNALPROCESSING”, the entireties of which are incorporated herein byreference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

This application relates generally to optical coherence tomography(OCT), and more specifically, to angiographic OCT.

2. Description of Related Art

Angiographic optical coherence tomography (OCT) is a technique thatvisualizes vasculature based on three dimensional (3D) OCT volumeinformation. The underlying concept of OCT angiography is that the bloodflow inside vasculature induces motion that manifests as changes inrelative phase and/or pixel intensity in OCT imaging over time. OCTangiography processes visualize such phase and/or intensity changes torepresent vasculature. Such changes are assumed to originate from bloodflow and are, therefore, assumed to represent vasculature. 3D OCT can beused for angiographic purposes, as it possesses sufficient resolutionfor visualization of capillary structures and it can providedepth-resolved information. Flow, and vasculature by extension, can bevisualized not only as an en-face projection, but also depth by depthor, more generally, cross-section by cross-section. Furthermore,different ranges of depth can be conveniently integrated to provideen-face angiographic visualizations corresponding to different zonesalong depth (e.g., superficial blood vessels, deep capillary plexus,choriocapillaris), all from a single 3D OCT scan process (includingthose involving repetitive scans, for example, as described below) witha scan time on the order of only several seconds. Compared withconventional angiography imaging modalities (e.g., fluoresceinangiography (FA), and indocyanine green angiography (ICGA)), OCTangiography does not require exogenous dye which can induce adversereactions in patients. In addition, the high signal to noise ratio (SNR)of OCT technology and high sensitivity and high contrast for flowdetection enable OCT angiography to provide noninvasive, and highresolution/fidelity visualization of vasculature in both transverse anddepth directions.

Generally, angiographic OCT techniques may be implemented by: (1)repetitively scanning each location within a 3D volume and analyzing themultiple repetitions at each scan location for motion; (2) incrementalstepping between locations (i.e., not repetitively scanning eachlocation), such that each location is sufficiently similar to theprevious location to enable motion detection analysis; and (3) scanningat a very high resolution in the fast axis, such that there is overlapbetween successive A-lines; therefore, rather than comparing betweencorresponding locations in B-scans, adjacent A-lines can be compared toevaluate motion. Variants of the above methods have also been proposed,such as measuring several A-lines and then repeating before movingonward within the B-scan.

One example approach is optical microangiography (OMAG), which utilizesboth OCT phase and magnitude information to deliver finely detailedangiographic images. Recently a variation of OMAG called IntensityDifferentiation, which does not utilize phase information, has beenproposed. Another example is split-spectrum amplitude-decorrelationangiography (SSADA), which uses only magnitude information in whichspectral data is split into chunks that are separately processed basedon an amplitude-decorrelation formula, and then later combined.

In OMAG, calculations are based on differences between intensity values.These difference calculations are implemented as subtractions betweenintensity terms, and in the case of complex operations, may be followedwith taking the magnitude of the result.

With SSADA, the spectral bandwidth is split into smaller equally-sizedbands. This is illustrated in FIG. 1, whereby the total bandwidth (BW)is split into four sub-bands (bw1, bw2, bw3, and bw4) to produce fourinterferograms I′(x,k′) corresponding to each of the four sub-bands. Foreach sub-band: (1) A window function is applied; (2) Images areconstructed; and (3) Angiographic calculations, using anamplitude-decorrelation formula, are performed between adjacent frames.Then, the decorrelations among all frame combinations are averaged.B-scans that might not match the other B-scans may be excluded. This canserve to reduce motion artifacts that manifest as bright lines that mayspan an en-face angiogram from one end to the other.

BRIEF SUMMARY OF THE INVENTION

According to one example, an angiographic OCT method comprisescalculating ratio-based values of OCT images generated from captured OCTdata of a subject volume, the OCT data being captured at a plurality oftimes and the values being calculated by comparing respective pixels ofthe OCT images at the plurality of times; generating angiographic imagesbased on the values; and displaying, rendering, and/or storing the OCTimages and/or the angiographic images, wherein when the values includeratio-based values, the ratio-based values are not further modified by anon-linear calculation.

In various embodiments of the above example, the ratio-based values arecalculated according to a function that receives, as a variable input, avalue corresponding to a ratio between two intensities; the valuecorresponding to the ratio is a difference between log-scale intensityinformation between two OCT images; the ratio-based values arerepresented by a ratio between two intensities; the ratio-based valuesare calculated by dividing first pixel values of an OCT image obtainedat a first time by second pixel values of an OCT image obtained at asecond time; the ratio-based values are substantially equivalent to orcorrespond to a ratio calculation of a pair or pairs of OCT images atthe plurality of times; the ratio-based values are calculated for OCTimages at at least two of the plurality of times; the method furthercomprises: averaging the ratio-based values for an X-Y position of theOCT images; comparing the averaged values to a criteria; and excludingratio-based values that do not meet the criteria; the averaging,comparing, and excluding are performed A-line by A-line; the methodfurther comprises filtering the captured data before generating the OCTimages, before generating the angiographic images, and/or beforedisplaying the OCT images and/or angiographic images, wherein the filtercharacteristics are customized based on the image to be generated ordisplayed by depth, depth size, or type of vasculature; the displayingincludes displaying at least one high-resolution OCT image and/or OCTangiography image, and at least one filtered OCT image and/or OCTangiography image; the method further comprises generating the OCTimages of the subject volume based on the captured OCT data; a partialspectrum of an OCT light source is used to generate at least one of theOCT images; OCT images are generated by applying a function tointerferograms, or from interferograms having envelopes, and wherein anequivalent noise bandwidth (ENBW) for generating structural OCT imagesis greater than the ENBW for generating angiographic OCT images; theENBW for generating angiographic OCT images is less than 1.23; theenvelopes are of interferograms immediately before a discrete Fouriertransform is applied; at least one of the values achieves a greatersensitivity to a decorrelation between OCT images at the plurality oftimes than a value determined according to

${1 - {\frac{1}{N - 1}\frac{1}{M}{\sum\limits_{n = 1}^{N - 1}\;{\sum\limits_{m = 1}^{M}\;\frac{{A_{n}( {x,z} )}{A_{n + 1}( {x,z} )}}{\lbrack {{\frac{1}{2}{A_{n}( {x,z} )}^{2}} + {\frac{1}{2}{A_{n + 1}( {x,z} )}^{2}}} \rbrack}}}}},$where N is the number of repeat B-scans, M is the number of spectralsplits, and An and Am are pixel values in subsequent images; the valuesare enabled or utilized only for pixels having a value greater than aminimum intensity threshold; the minimum intensity threshold isdetermined by selecting a pixel intensity at a predetermined percentileof pixel intensities according to a histogram or sorted list of pixelsof at least a portion of the OCT images; the pixel intensities onlycorrespond to a background signal of the OCT images; the pixelintensities correspond to more than a background signal of the OCTimages; A-scans of the OCT data are captured at a rate less than 1 MHz;and/or A-scans of the OCT data are captured at a rate between 25 kHz and800 kHz.

According to another example, an angiographic OCT method comprises:calculating angiographic deviation values of OCT images generated fromcaptured OCT data of a subject volume, the OCT data being captured at aplurality of times and the values being calculated by comparingrespective pixels of the OCT images at the plurality of times;generating angiographic images based on the values; and displaying,rendering, and/or storing the OCT images and/or the angiographic images,wherein when the values include ratio-based values, the ratio-basedvalues are not further modified by a non-linear calculation.

In various embodiments of the above example, the angiographic deviationvalues are calculated between images at the first time and at the secondtime; the angiographic values are calculated for OCT images at at leasttwo of the plurality of times; the method further comprises: averagingthe angiographic deviation values for an X-Y position of the OCT images;comparing the averaged values to a criteria; and excluding angiographicdeviation values that do not meet the criteria; the averaging,comparing, and excluding are performed A-line by A-line; the methodfurther comprises filtering the captured data before generating the OCTimages, before generating the angiographic images, and/or beforedisplaying the OCT images and/or angiographic images, wherein the filtercharacteristics are customized based on the image to be generated ordisplayed by depth, depth size, or type of vasculature; the displayingincludes displaying at least one high-resolution OCT image and/or OCTangiography image, and at least one filtered OCT image and/or OCTangiography image; the method further comprises generating the OCTimages of the subject volume based on the captured OCT data; a partialspectrum of an OCT light source is used to generate at least one of theOCT images; OCT images are generated by applying a function tointerferograms, or from interferograms having envelopes, and wherein anequivalent noise bandwidth (ENBW) for generating structural OCT imagesis greater than the ENBW for generating angiographic OCT images; theENBW for generating angiographic OCT images is less than 1.23; theenvelopes are of interferograms immediately before a discrete Fouriertransform is applied; at least one of the values achieves a greatersensitivity to a decorrelation between OCT images at the plurality oftimes than a value determined according to

${1 - {\frac{1}{N - 1}\frac{1}{M}{\sum\limits_{n = 1}^{N - 1}\;{\sum\limits_{m = 1}^{M}\;\frac{{A_{n}( {x,z} )}{A_{n + 1}( {x,z} )}}{\lbrack {{\frac{1}{2}{A_{n}( {x,z} )}^{2}} + {\frac{1}{2}{A_{n + 1}( {x,z} )}^{2}}} \rbrack}}}}},$where N is the number of repeat B-scans, M is the number of spectralsplits, and An and Am are pixel values in subsequent images; the valuesare enabled or utilized only for pixels having a value greater than aminimum intensity threshold; the minimum intensity threshold isdetermined by selecting a pixel intensity at a predetermined percentileof pixel intensities according to a histogram or sorted list of pixelsof at least a portion of the OCT images; A-scans of the OCT data arecaptured at a rate less than 1 MHz; A-scans of the OCT data are capturedat a rate between 25 kHz and 800 kHz; and/or the angiographic deviationvalues are log-normal deviation values or geometric standard deviationvalues.

According to another example, a method comprises: calculating values ofOCT images generated from captured OCT data of a subject volume at aplurality of times; and generating angiographic images based on thevalues.

In various embodiments of the above example, the values are ratio-based,angiographic deviations (e.g., log-normal deviations, geometric standarddeviations), or combinations thereof; the values are calculated bycomparing respective pixels of the OCT images at the plurality of times;the values are calculated according to a function that receives, as avariable input, a value corresponding to a ratio between twointensities; the value corresponding to the ratio is based on adifference between log-scale intensity information between two images;the values are not further modified by a non-linear calculation; aratio-based value is not further modified by a non-linear calculation;the values can be represented by a ratio between two intensities; thevalues are calculated by dividing the pixels of an OCT image at a firsttime by the pixels of an OCT image at a second time, and theangiographic deviation values are calculated between images at a firsttime and at a second time; the values are calculated according to

${r( {x,z} )} = {{abs}( {\log\lbrack \frac{A_{m}( {x,z} )}{A_{n}( {x,z} )} \rbrack} )}$or r(x, z)=abs(log[A_(m)(x, z)]−log [A_(n)(x, z)]), where abs( ) is anabsolute value calculation, log( ) is a logarithm in any base, and m andn refer to any two images where m does not equal n; the values aresubstantially equivalent to or corresponding to a ratio calculation of apair or pairs of OCT images at the plurality of times; the values arecalculated for OCT images at least two of the plurality of times, theplurality of times being determined by any permutation of the pluralityof times; the permutation is arbitrarily selected; the method furthercomprises averaging the ratio-based or angiographic deviation values foran X-Y position of the OCT images; comparing the averaged values to acriteria; and excluding ratio-based values that do not meet thecriteria; the averaging, comparing, and excluding are performed A-lineby A-line; the method further comprises averaging the ratio-based orangiographic deviation values; the ratio-based values or angiographicdeviation values are averaged over a range within an A-line or acrossA-lines; the method further comprises displaying the OCT images and/orthe angiographic images; the method further comprises filtering thecaptured data before generating the OCT images, before generating theangiographic images, and/or before displaying the OCT images and/orangiographic images; the filter characteristics are customized based onthe image to be generated or displayed by depth, depth size, or type ofvasculature; the display includes at least a 3D rendering visualizationor high-resolution OCT image and/or OCT angiography image, and at leastone filtered OCT image and/or OCT angiography image; the OCT imageand/or OCT angiography image is an en-face image or B-scan; the methodmay instead comprise: capturing OCT data of a subject volume, the OCTdata being captured at a plurality of times for at least one position inthe subject volume; and generating OCT images of the subject area at theplurality of times; in generating the OCT images, no windowing function,a windowing function having an equivalent noise bandwidth (ENBW) lessthan 1.23, spectral reshaping having an ENBW less than 1.23, or anycombination thereof is applied; structural OCT images are generated frominterferograms of the OCT data having envelopes with an equivalent noisebandwidth (ENBW) greater than or equal to a predetermined level, and/orimages for angiographic calculations are generated from interferogramsof the OCT data having envelopes with an ENBW less than thepredetermined level, wherein the envelopes are of interferogramsimmediately before a discrete Fourier transform is applied; a partialspectrum is used to generate the OCT images; structural OCT images areprocessed with a first set of parameters and images for angiographiccalculations are processed with a second set of parameters; the firstset of parameters includes a windowing function with an ENBW greaterthan or equal to 1.23, and the second set of parameters includes, awindowing function having an ENBW less than 1.23, spectral reshapinghaving an ENBW of less than 1.23, a combination thereof, or does notinclude a windowing function; at least one of the values achieves agreater sensitivity to decorrelation than a value determined accordingto

${1 - {\frac{1}{N - 1}\frac{1}{M}{\sum\limits_{n = 1}^{N - 1}\;{\sum\limits_{m = 1}^{M}\;\frac{{A_{n}( {x,z} )}{A_{n + 1}( {x,z} )}}{\lbrack {{\frac{1}{2}{A_{n}( {x,z} )}^{2}} + {\frac{1}{2}{A_{n + 1}( {x,z} )}^{2}}} \rbrack}}}}},$where N is the number of repeat B-scans, M is the number of spectralsplits, and A_(n) and A_(m) are pixel values in subsequent images; thevalues are calculated only for pixels having a value greater than aminimum intensity threshold; the minimum intensity threshold iscalculated relative to a weak foreground signal; the minimum intensitythreshold is determined by selecting a pixel intensity at apredetermined percentile of pixel intensities according to a histogramor sorted list of at least a portion of the OCT images; the percentileis between 25-30% or 50-75% when the pixel intensities are ordered fromleast to greatest; the minimum intensity threshold is determinedautomatically according to predetermined pixel intensity percentile;A-scans are acquired at a rate less than 1 MHz; A-scans are acquired ata rate between 25 kHz and 800 kHz; and/or the angiographic deviationvalues are log-normal deviation values or geometric standard deviationvalues.

In still another example, an OCT system implements any of the aboveexample methods. In various embodiments of such a system, a user ispresented with angiographic data or images generated from at least twocalculations or wherein the user is presented with an option to selectwhich of at least two calculations to use to generate angiographic dataor images.

It is noted that any combination of the above examples and embodimentsthereof is within the scope of the present disclosure. The variousembodiments of each example are not intended to be limited to thatexample, and may be applied to other examples or variations of thoseexamples.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWING

FIG. 1 illustrates a diagram of a Split-Spectrum Amplitude-DecorrelationAngiography (SSADA) technique;

FIG. 2 illustrates a representative spectral domain optical coherencetomography (SD-OCT) system;

FIG. 3 illustrates a representative swept-source optical coherencetomography (SS-OCT) system;

FIG. 4 is a flowchart of a technique described herein;

FIG. 5 is a flowchart for calculating a ratio-based value according totwo methods;

FIG. 6 is a flowchart for quantifying motion artifacts;

FIG. 7 illustrates a comparison of the results of a rectangular windowand a Hann window;

FIG. 8 is a flowchart for determining a minimum intensity threshold;

FIG. 9A illustrates comparative angiography images for a SSADA-liketechnique and techniques described herein;

FIG. 9B illustrates comparative angiography images for standarddeviation interframe calculations and techniques described herein; and

FIG. 10 is a plot that graphically demonstrates the relative sensitivityadvantage of a ratio-based approach over amplitude decorrelation.

DETAILED DESCRIPTION OF THE DRAWINGS

Certain terminology is used herein for convenience only and is not to betaken as a limitation on the present invention. Relative language usedherein is best understood with reference to the drawings, in which likenumerals are used to identify like or similar items. Further, in thedrawings, certain features may be shown in somewhat schematic form.

It is also to be noted that the phrase “at least one of”, if usedherein, followed by a plurality of members herein means one of themembers, or a combination of more than one of the members. For example,the phrase “at least one of a first widget and a second widget” means inthe present application: the first widget, the second widget, or thefirst widget and the second widget. Likewise, “at least one of a firstwidget, a second widget and a third widget” means in the presentapplication: the first widget, the second widget, the third widget, thefirst widget and the second widget, the first widget and the thirdwidget, the second widget and the third widget, or the first widget andthe second widget and the third widget. Finally, the term“substantially,” if used herein, is a term of estimation.

It should be noted that the following description applies to Fourierdomain OCT implementations, including both spectral domain OCT (SD-OCT)and swept-source OCT (SS-OCT) in any wavelength/frequency band. FIGS. 2and 3 illustrate SD-OCT and SS-OCT systems, respectively, as aregenerally understood in the art. The SD-OCT examples provided herein arefrom about the 850 nm band and the SS-OCT examples provided herein arefrom about the 1050 nm band. Additionally, although for convenience thefollowing disclosure references images and scan patterns in terms ofhorizontal B-scans in the X-Z plane, images and scans may have anyarbitrary orientation. For example, the angiographic scans can be 3Dhorizontal scans, 3D vertical scans, 3D diagonal, raster scans, crossscans, circumpapillary, radial scans, or the like. Scan lines can be ofarbitrary orientation, length, and curvature, and do not have to followregular patterns or orientations relative to those in other neighboringscan locations.

It is also noted that although FIGS. 2 and 3 illustrate representativeOCT systems, such specific systems are not required as part of thepresent disclosure. Rather, the present disclosure also pertains to datathat has already been captured and/or OCT images that have already beengenerated. OCT images as used herein refer to any images formed based onOCT captured data, for example, A-scans, B-scans, and C-scans. Such datamay have been captured with any type of OCT system, includingtime-domain OCT, or even other imaging modalities. In other words, theaspects described herein can also apply to fully processed OCT images.Accordingly, these aspects can be independent of the underlying OCTsystem optical design or other imaging modality.

In SSADA, a degree of decorrelation is calculated according to:

${\overset{\_}{D}( {x,z} )} = {1 - {\frac{1}{N - 1}\frac{1}{M}{\sum\limits_{n = 1}^{N - 1}\;{\sum\limits_{m = 1}^{M}\;\frac{{A_{n}( {x,z} )}{A_{n + 1}( {x,z} )}}{\lbrack {{\frac{1}{2}{A_{n}( {x,z} )}^{2}} + {\frac{1}{2}{A_{n + 1}( {x,z} )}^{2}}} \rbrack}}}}}$where N is the number of repeat B-scans, and M is the number of spectralsplits. This equation produces values between 0 and 1 indicating adegree of decorrelation. In other words, a low value indicates a highdegree of correlation between each set of values, and a high valuecorresponds to a low degree of such correlation. A high degree ofdecorrelation is then associated with motion and, by extension, withflow. In practice, SSADA suffers from a number of deficiencies. Forexample, the amplitude-decorrelation formula has traditionally limitedthe decorrelation calculations to be between adjacent frames. In otherwords, the interframe calculations in SSADA are limited to adjacentframe combinations. Additionally, because the OCT images are blurred inan early stage of processing, the angiographic data reflects the lowerresolution (blur), and some features that otherwise may have beenresolvable in the original data may no longer be distinguishable.

It is now recognized that a ratio of frames may be used to quantifymotion. For example, the ratio may be determined according to:

$r = \frac{A_{n}( {x,z} )}{A_{m}( {x,z} )}$where m and n refer to arbitrary frames within a set of frame capturesfor a given scan location.

In view of this recognition, a ratio-based and/or angiographic deviationcalculation is used to determine change or motion according to a firstaspect of a technique described herein. According to a second aspectdescribed herein, arbitrary interframe permutations are used todetermine change or motion. According to a third aspect describedherein, post-calculated, non-linear results for projection visualizationare averaged. According to a fourth aspect described herein, poormatches are eliminated on an A-line by A-line basis. According to afifth aspect described herein, windowing functions may be customized toimprove results. A sixth aspect described herein relates to the use ofpartial spectrums. A seventh aspect described herein relates toutilizing a minimum intensity threshold for determining which pixels touse in a ratio-based calculation.

FIG. 4 illustrates a flowchart of a technique described herein accordingto the above aspects. It is noted that the various steps therein areoptional, but each may be associated with improved results. According toa first step 400, spectral data is scanned and captured. Generally, atypical scan pattern may cover a 3 mm×3 mm area with 2-8 repetitions perscan line location for 512-1024 total B-scans (64 to 512 B-scanlocations typically). It should be noted that such characteristics arenot intended to be limiting and parameters such as the size of the scanpattern, repetitions per scan line, total number of B-scans, and totalnumber of locations may be larger or smaller without deviating from thescope of the present disclosure.

Next, OCT images are generated from the captured data at step 402.Generating OCT images includes conventional processing to convertspectral (interferogram) data into OCT images. This may include, but isnot limited to, one or more of rescaling (for example, with respect toSD-OCT data); fixed pattern noise (FPN) removal; numerical dispersioncompensation (NDC); windowing; spectral reshaping; a discrete Fouriertransform (DFT); magnitude and/or phase calculations; and/or logarithmconversion or other transform of magnitude data. It is noted that thevarious described steps that follow generally assume OCT intensity datain linear scale. Therefore, if data has been converted to log scale, itmight be desirable to first convert back to linear scale for ratiocalculations. Nevertheless, equivalent or corresponding logarithmicscale calculations may also be used.

In another optional step, frame repetitions at each scan location areregistered with each other at step 404. In addition to aiding theangiographic process, the registration of the multiple frames, incombination with an averaging process, enables the generation ofhigh-quality (improved SNR) B-scans that are potentially useful both fordisplay purposes and segmentation purposes. The registration process mayhave the effect of reducing motion artifacts in the angiographicoutputs, if saccadic or microsacaddic motion has occurred.

Before generating angiograms at step 406, OCT images may bepreprocessed. For example, because angiography calculations are highlysuspect to noise (e.g., Gaussian background or speckle noise), filtersmay be used to either disable or stabilize angiography calculations, forexample in those pixels in which the signal intensity is relatively lowcompared to the background electrical noise. Filters such as a Gaussianfilter may be utilized to filter data along A-lines, although a smalldegree of filtering across A-lines may also be applicable depending, forexample, on the resolution of the scan. Several such methods can beused, alone or in tandem. In one example method, angiographiccalculations may be disabled for pixels that do not meet a minimumintensity threshold level, either in the averaged composite image, or inthe individual OCT frame. This minimum intensity threshold may beapplied to individual frames, registered frames, averaged frames, and/orother forms of the captured data. According to an example application,pixel locations not meeting the minimum intensity threshold level may beassigned a value (e.g., 0 or some arbitrary value) as the angiographicresult. Alternatively, the particular frame containing the affectedpixel may be excluded from interframe calculations, for example, withrespect to the given pixel. In another example, if any pixel intensityis below the threshold level, the pixel intensity may be saturated to alevel of the threshold. In still another example, adding a “DC offset”to image pixel intensities can limit the degree that variations, whichmay be due to noise, affect the angiography calculations. When apositive constant DC offset level is added to both numerator anddenominator in a ratio calculation, the result will tend to bemoderated. In still other examples, a ratio may be calculated for pixelswith signal intensities below the minimum intensity threshold, but onlyafter all pixel values are raised to a predetermined level. This mayhave the effect of at least partially overcoming deconstructive speckleand bringing the ratio closer to unity.

Following preprocessing, selected (or potentially all) framecombinations at a particular scan location are processed to generateangiograms at step 406. Interframe calculations are applied on a pixelby pixel basis (e.g., in pairs of frames). In addition to the SSADAamplitude decorrelation calculation discussed above, other functionssuch as absolute difference, standard deviation, variance, coefficientof variation, maximum, median, geometric median and minimum are alsoconceivable. These functions may be applied in pairs of frames, perpixel, and/or combinations thereof. For example standard deviation andcoefficient of variation, calculations may be performed among all framesto be included in a single calculation (per pixel) rather than beingperformed in a pair-wise manner between frames, they. Thus, the valuefor each pixel in the final, composite image represents an average amongthe individual calculations corresponding to the potentially multipleinterframe combinations. These calculations may all be based on thepost-registered images.

According to the first aspect, OCT angiographic results described hereinare produced by a ratio-based calculation, thereby allowing sharpvisualization of vasculature across the depths of the retina. Some ratiocalculation methodologies require a one-sided ratio as an input. Aone-sided greater ratio is a ratio of A₁ to A₂ if A₁≥A₂, or the ratio ofA₂ to A₁ if A₂>A₁, where A₁ and A₂ are pixel values of a given locationin two images (at two points in time). Similarly, a one-sided lesserratio (the inverse of the one-sided greater ratio) is the ratio of A₁ toA₂ if A₁≤A₂, or the ratio of A₂ to A1 if A₂<A₁. Therefore, the one-sidedgreater ratio will always be greater than or equal to one, and theone-sided lesser ratio will always be between 0 and 1 inclusive, as longas A₁ and A₂ are both positive. The two types of one-sided ratios can beconverted to one another by taking the reciprocal, as long as neither A₁nor A₂ were zero. Either of these ratios can be pre-defined to have afixed value of either one or some other value, should either or both ofthe A₁ or A₂ intensity values be equal to zero. The directionality ofthe ratio has no particular meaning.

It is noted that a one-sided ratio may also result from calculationsother than simple division. For example, the ratio may result fromtaking the absolute value as described below with respect to the“log-ratio” method (effectively corresponding to a one-sided greaterratio). According to another example, the ratio may be the result ofsubtracting log-scale intensity information between images (as dividingtwo values and taking the logarithm is equivalent to subtracting twolog-scale values; a one-sided ratio if the absolute value is taken). Inthis way, the ratio-based value can be a value other than a simpledivision of intensities. For example, the ratio-based values may begenerated by operations other than division, including multiplicationsand exponentials (e.g., squaring). These various operations may beperformed before or as part of the ratio-based calculation. In doing so,the operations do not necessarily affect a final sensitivity. Stillother transformations may be applied following the ratio-basedcalculation.

In methodologies utilizing a one-sided ratio calculation, the calculatedvalue may be saturated at a given level at an upper or lower range. Itis possible to apply a fixed saturation level (e.g., a saturation levelof 2, where one-sided greater ratio results are typically less than 2),such that constraining the result range may reduce storage requirementsand improve data processing and visualization processing speeds.

The ratio value may be calculated according to any number of methodswithout diverting from the scope of the present disclosure. In a firstapproach, a “ratio as is” is calculated as a one-sided greater ratiovalue without any additional calculations or transformations.Accordingly, the “ratio as is” methodology directly compares a pixelvalue at a given location between two images (or frames). The analysiscan be performed on a one-by-one location-by-location basis where bothimages are represented in a linear scale.

Two other approaches to the ratio-based calculations are illustrated inFIG. 5. It is to be noted that the calculations illustrated in FIG. 5assume images in linear scale. According to a first step of thesecalculations 500, the pixel values in one image are divided (therebyforming ratios) by those of the other image in the frame pair on aone-by-one location-by-location basis, where both images are representedin linear scale. If a pixel in the other image (the denominator) has avalue of 0, then the calculated pixel result may be assigned anarbitrary value. It is noted that the ratio is a one-sided variable andthe directionality of the ratio has no particular meaning. Thus,according to an “inverted ratio”, at step 502 the reciprocal is takenfor any pixels in which the ratio is initially greater than 1, so thatthe resulting ratios are between 0 and 1. This results in a one-sidedlesser ratio, which can be subtracted from 1 at step 504 to generate aninverted ratio value. This approach may be generalized according to:

${r( {x,y} )} = {1 - {\frac{1}{N}{\sum\limits_{i,j}^{N}\frac{\min( {{I_{i}( {x,y} )},{I_{j}( {x,y} )}} )}{\max( {{I_{i}( {x,y} )},{I_{j}( {x,y} )}} )}}}}$where I(x, y) is the OCT signal intensity, N is the number of scannedB-scan combinations at the given location, and i and j represent the twoframes within any given combination of frames. An averaging functioncould alternatively be implemented by any number of operations,including a median or other quantile, minimum, maximum, or geometricmean, for example, as described below.

Similarly, according to a “ratio minus one” method, for pixels in whichthe ratio is less than 1, the reciprocal may be taken at step 506 shouldit be desired to obtain ratio values between 1 and infinity. Thisresults in a one-sided greater ratio, from which 1 can be subtracted atstep 508 to generate a ratio minus one value. This approach may also begeneralized in a similar manner to the “inverted ratio” method.

In another approach, a “log-ratio” method, the ratio based calculationis performed according to:

${r( {x,z} )} = {{abs}( {\log\lbrack \frac{A_{m}( {x,z} )}{A_{n}( {x,z} )} \rbrack} )}$where the ratio is found by taking the absolute value of the log of theratio of a frame pair. This is also equivalent to taking the logarithmof the one-sided greater ratio. The logarithm can be in any base, and mand n refer to any two images (where m does not equal n). In addition, athreshold can be optionally applied to the log-ratio result, such that,for example, any absolute values greater than 1 are saturated at thatlevel. The logarithm calculation may be performed in any base becausethe relative results will be equivalent. Still, depending on theparameterization of the display step 410 (discussed below), the choiceof logarithm base could be impactful. However, the display processingmay be normalized to counteract the effect of the selected base.

It is noted that other variations of these calculations are conceivablewithout departing from the scope of the present disclosure. For example,one may take the logarithm of images before calculation, and thenperform a subtraction rather than a division. This could be followed bytaking the absolute value. Given the characteristics of logarithms, sucha calculation would be equivalent to the above calculation. In otherwords, as noted above, dividing two values and taking the logarithm isequivalent to subtracting two log-scale values and taking the absolutevalue generates a one-sided ratio. For example:r(x, z)=abs(log[A _(m)(x, z)]−log[A _(n)(x, z)])However, because calculating the ratio with logarithms is not acalculation in the linear scale, performing further non-linearstatistical calculations can greatly lower the relative sensitivity toareas with lower flow. For example, if the above calculation werefurther squared, the relative sensitivity would be squared. For valuesless than one (e.g., 0.011 as illustrated in Table 1), the squared valuewould be smaller by about a factor of 100 (0.011²=0.000121). Suchsensitivity is comparatively worse than linear calculations andamplitude decorrelation methods.

In this way, it is noted that calculations (e.g., functions) thatutilize a ratio value as an input are also within the scope of thepresent disclosure. Such functions may take the form of f(r). However,still other functions may that do not explicitly recite ratio as aninput variable are considered within the scope of the presentdisclosure. For example, a function defined as f(A₁, A₂)=(A₁−A₂)/A₁divided through by A₁ in the denominator transforms to the function tof(r)=1−r or 1−(1/r), depending on the definition of r. Accordingly, thisfunction can be represented as a function of the ratio as is to beunderstood herein. The above example is not intended to be limiting andstill other similar functions are understood to be within the scope ofthe present disclosure. In still other embodiments, utilizing a valuerepresentative of a ratio is also within the scope of the presentdisclosure. For example, a magnitude of the ratio of two intensitiesmultiplied by a phase term may be represented as a ratio. Similarly, forexample, the magnitude difference between two log-scale intensitiesmultiplied by a phase term is also within the scope of the presentdisclosure.

It is also noted that the above ratio calculations and the use of theabove ratios can accommodate intensity data in the complex realm. Insuch cases, it is possible to take the magnitudes of each intensitybefore calculating the ratio, or calculate the complex ratio followed bya magnitude calculation. When in the complex realm, it is conceivable toutilize the complex conjugate (or other similar numericaltransformations) for either or both values in the ratio calculation.

Furthermore, the ratio can be generalized and expanded to include anangiographic deviation, such as a geometric standard deviation orlog-normal deviation (a standard deviation of a log-normaldistribution). Still further, the angiographic deviation can begeneralized and expanded to include calculations (e.g., non-ratiocalculations, such as a variance) that provide results similar orequivalent to standard deviations. For example, taking the average of aseries of pairwise absolute differences (or differences to thecollective mean) will roughly correspond to the (arithmetic) standarddeviation or absolute deviation, and taking the average of a series ofpairwise ratio measures will roughly correspond to the geometricstandard deviation, for example, with respect to angiographicvisualizations as discussed herein. Therefore, taking a standarddeviation is roughly analogous to taking the sum of the absolute valuesof pairwise differences, and taking the geometric deviation of thecorresponding pixel values in the component image frames is roughlyanalogous to the pairwise ratio methodology discussed previously and canachieve similar results. It is noted that ratios, by their nature, arecalculations based on pairs of data; geometric standard deviations canbe performed using any number of frames.

The angiographic deviation is also understood to be a log-normaldeviation. For example, a log-normal deviation results from log-scaleimages where a standard deviation is calculated among all frames foreach pixel location of the log-scale images. This log-normal deviationcan produce results similar to a geometric standard deviation taken onlinear scale images, and thus can also produce results similar to takingthe difference of logarithms, as discussed above. An angiographicdeviation may also refer to still other calculations that produceresults similar or equivalent to any of the above describedcalculations, such as an absolute deviation and/or variance. It is notedthat the above-described angiographic deviations can be used in additionto, or alternatively to, the above-described ratio-based methodologies.

Nevertheless, the calculations can be flexibly applied withoutsignificantly affecting the results. For example, the arithmetic mean oranother averaging technique could be utilized in place of a geometricmean. Similarly, the ratio calculations could be implemented using thepixel-wise ratios between each image frame and a collective mean image(either an arithmetic or geometric mean, or similar averagingtechnique), and averaging across results (also arithmetic or geometricmean, or similar averaging technique). The order of the geometricstandard deviation calculation could also be altered. For example, thecomponent images can be multiplied by any given factor or the imagepixels may be transformed, for example, by a power operation.

While the above examples relate to inputting a ratio or pixel value toan algorithm, it is also possible to implement the above calculations ina more digital form. For example, a lookup table may be utilized, wherepre-determined outputs corresponding to given inputs are stored, e.g.,in memory of the system on which the present disclosure is implemented.Such a table could also be stored remotely.

The following table illustrates a comparison of sensitivities (indicatedrelative to the values of other rows in the same column, rather thanacross columns) of the above described log-ratio, inverted ratio, andratio minus one results to the amplitude decorrelation calculation overa range of one-sided greater ratio values (left column).

TABLE 1 Comparison of relative sensitivities within various calculationsOne Sided Log-Ratio Inverted Ratio Ratio Minus 1 Amplitude Greater RatioMethod Method Method Decorrelation 1.000 0.000 0.000 0.000 0.0000 1.0250.011 0.024 0.025 0.0003 1.050 0.021 0.048 0.050 0.0012 1.100 0.0410.091 0.100 0.0045 1.250 0.097 0.200 0.250 0.0244 1.500 0.176 0 3330.500 0.0769 2.000 0.301 0 500 1.000 0.2000 3.000 0.477 0.667 2.0000.4000 4.000 0.602 0.750 3.000 0.5294 5.000 0.699 0.800 4.000 0.61547.500 0.875 0.867 6.500 0.7380 10.000 1.000 0.900 9.000 0.8020

As can be seen, the ratio-based methods are more sensitive to ratioscloser to 1 (e.g., the 1.025-1.10 one-sided greater ratio rows of thetables) than is amplitude decorrelation. The result of this is increasedsensitivity to and linearity with respect to less flow. The results forthe ratio-based methods are also significantly greater when viewedrelative to greater flows (higher one-sided greater ratio values). Asnoted above, the linear ratio methods (Inverted Ratio and Ratio Minus 1)provide better relative sensitivity characteristics at low andmoderate-to-high flows than the Log-Ratio method. It should be notedthat this table, and all following tables, could alternatively bepresented in terms of one-sided lesser values.

The following tables illustrate relative “within-method” results for agiven function when evaluated relative to a stated reference ratio. Inother words, the following tables illustrate the sensitivity within asingle method at different flow levels as compared to the referenceratio level. For example, the amplitude decorrelation value of 80.02 fora one-sided greater ratio value of 1.025 is obtained by: 0.0244/0.0003(accounting for rounding) as found in Table 1. Accordingly, a low valueindicates better sensitivity of low-flow detection.

TABLE 2 Relative within-method sensitivity of low flow based on areference ratio of 1.250 One Sided Inverted Ratio Greater Log-RatioRatio Minus 1 Ratio Amplitude Ratio Method Method Method As IsDecorrelation 1.025 9.04 8.20 10.00 1.22 80.02 1.050 4.57 4.20 5.00 1.1920.51 1.100 2.34 2.20 2.50 1.14 5.39 1.250 1.00 1.00 1.00 1.00 1.00

TABLE 3 Relative within-method sensitivity of low flow based on areference ratio of 1.500 One Sided Inverted Ratio Greater Log-RatioRatio Minus 1 Ratio Amplitude Ratio Method Method Method As IsDecorrelation 1.025 16.42 13.67 20.00 1.46 252.38 1.050 8.31 7.00 10.001.43 64.69 1.100 4.25 3.67 5.00 1.36 17.00 1.250 1.82 1.67 2.00 1.203.15 1.500 1.00 1.00 1.00 1.00 1.00As can be seen, each of the ratio-based methodologies achieves asignificantly greater sensitivity of low flow detection than amplitudedecorrelation.

In comparing the calculations described herein with amplitudedecorrelation, the comparison may be made based on the same number ofsplit spectrums. As noted above, SSADA is calculated in part based onthe number of spectral splits of the light source; and as the variouscalculations described herein can also utilize split spectrumprocessing, the most relevant comparisons compare sensitivities of eachmethod utilizing the same number of spectrum splits. For example, thesensitivity of an amplitude decorrelation calculation using a spectrumsplit into two bands finds its relative comparison in other calculationsalso using two split bands.

The following tables illustrate relative advantages of ratio-basedmethodologies over amplitude decorrelation based on the “within-method”sensitivity of low flows. In other words, the following tablesdemonstrate the advantage of the ratio-based calculations using directcomparisons to the results from corresponding amplitude decorrelationcalculations. For example, the “ratio as is” value of 65.62 for aone-sided greater ratio value of 1.025 for a reference ratio of 1.250 isobtained by: 80.02/1.22 (accounting for rounding) as found Table 2.Accordingly, larger values indicate a stronger relative advantage withrespect to amplitude decorrelation.

TABLE 4 Relative advantage over amplitude decorrelation for a referenceratio of 1.250 One Sided Log-Ratio Inverted Ratio Ratio Minus 1 GreaterRatio Method Method Method Ratio As is 1.025 8.36 9.76 8.00 65.62 1.0504.48 4.88 4.10 17.23 1.100 2.30 2.45 2.16 4.74 1.250 1.00 1.00 1.00 1.00

TABLE 5 Relative advantage over amplitude decorrelation for a referenceratio of 1.500 One Sided Log-Ratio Inverted Ratio Ratio Minus 1 GreaterRatio Method Method Method Ratio As is 1.025 15.37 18.47 12.62 172.461.050 7.78 9.24 6.47 45.28 1.100 4.00 4.64 3.40 12.47 1.250 1.74 1.891.58 2.63 1.500 1.00 1.00 1.00 1.00

Some implementations of the present disclosure may simultaneouslysupport calculating different numerical measures corresponding to motionvariation. For example, each (or any two) of the measures in the abovetables could be simultaneously calculated with the results available toa user. Thus, the user may be shown similar calculations with differentdegrees of sensitivity and noise characteristics that may be selected asdesired. In other embodiments, an interface could be provided thatallows the user to select which one (or more than one) of the multiplecalculations to perform. While the above table discloses a few ratiomethods and amplitude decorrelation, it is noted that these calculationsare not intended to be limiting. For example, other calculations mayinclude variance, standard deviation, coefficient of variation, absolutedifference, and the like. More generally, it is noted that the abovecalculations are based on arithmetic differences and arithmeticdeviation, whereas ratio and geometric deviation calculations are basedon geometric differences and deviations. Therefore, providing bothgeometric and arithmetic calculation results simultaneously to a usermay provide independent, useful information.

As discussed above, interframe combinations are based on those framesthat are scanned consecutively (adjacent in time). Such combinationshave a minimal separation of time, allowing for high flow rates to becaptured via the interframe calculation, which may yield highcalculation sensitivity. Additionally with such combinations, frames canbe more likely optimally matched to one another both with and withoutregistration (keeping in mind that the eye is frequently in motion).Different time separations can uncover or emphasize differentinformation within the resulting angiograms. For example, longer timeintervals allow for visualization of slower flow. However, suchinterframe calculations are still fixed separations in time. Further,given eye motion (e.g., including saccades, microsaccades, and bulkmotion that might in some cases affect the cornea, pupil, and vitreousin addition to the retina) and possibly other distortions in the imagingprocess (e.g., including phase instability and/or positioning errorwithin the OCT system), the flexibility to include arbitrarycombinations of frames can improve results by making calculationsavailable when there otherwise might be none (or very limited).

Thus, according to the second aspect described herein, any arbitrarypermutation of interframe combinations, regardless of their timeseparation, may be used to determine the above ratio-based calculation.For example, with the case of four repetitions, only those separated byone frame (leading to three combinations of N and N+1; N+1 and N+2; andN+2 and N+3), those separated by two frames (N and N+2; and N+1 andN+3), those separated by three frames (N and N+3), or any arbitrarycombination of any of these pairings (that may or may not include allthe pairings for a given frame separation) may be utilized. Therefore,if all frame combinations were to be used in this four repetitionexample scenario, there would be a total of six different interframecombinations. However, more generally any of the 63 possiblepermutations that include any number of these six different interframecombinations (still in this four repetition example scenario) could beselected. That is, 6(N=1)+15(N=2)+20(N=3)+15(N=4)+6(N=5)+1(N=6)=63.

Referring back to FIG. 4, following angiogram calculation, the next step408 includes boundary segmentation. Segmentation may be performed in atraditional manner, and may follow any of three permutations forangiographic 3D OCT volumes. First, segmentation of the registered andaveraged frames (that represent a combination of the multiplerepetitions at each scan location) may be advantageous due to theimproved SNR associated with these images. Second, segmentation of theindividual, non-averaged frames could be advantageous as results fromindividual frames could be used to detect and correct errors in othercorresponding (or even nearby) frames. This may be performed based onthe registered frames. Third includes segmentation of only thosenon-averaged frames that served as the templates for the registrationprocess.

According to the third aspect described herein, angiographic results maybe filtered at step 412, in part, to improve signal to noise ratio (SNR)in angiographic projection images and other displays. According to oneexample, an optional filter may be applied over the pixels within eachA-line representing angiographic results. Such a filter could utilize,as an example, a Gaussian transfer function, or it could also beimplemented via a moving average function, although such examples shouldnot be seen as limiting as any kind of filter could be utilized.Depending on the resolution of the scan, the filter may also extendacross A-lines.

The associated improvement in SNR is at least partially attributable tothe fact that the ratio calculation is non-linear in nature (e.g., it istypically not linear to the pixel intensity values in any of theindividual image frames used to generate the ratio result). Then, bysmoothing and/or averaging the ratio results (or any results based on anon-linear calculation for that matter), the SNR of the compositeangiographic results can be improved. It should be noted that due to thenon-linear nature of the ratio as well as some other angiographiccalculations (including amplitude decorrelation), this type offiltering/smoothing/averaging will be more impactful towardsangiographic SNR improvements than is filtering precursor OCT images ina similar manner (as described above). In other words, it may actuallybe deemed desirable to leave OCT images in the highest resolutionpossible, and then apply the filter/smoothing/averaging step at thispoint to the angiographic output data, thereby achieving a best casescenario of high resolution structural and angiographic data while alsobeing able to demonstrate filtered results in terms of projection views.

In one embodiment of the third aspect, a Gaussian filter with a sigma ofapproximately 8 microns is utilized, although it should be noted thatthis filter can be narrower or wider while achieving similar results andstaying within the scope of the present disclosure. This filter mayalso, or alternatively, be applied as a pre-processing step to anyprojection visualizations. Thus, the filter will not necessarily affectthe base data results and/or the high-resolution display(s).Additionally, it is noted that the filter parameters (e.g., type andlength) may be customized to the depth and type of the vasculature beingdisplayed. For example, projections covering a wide depth or of largervasculature may justify larger filter sizes with broader bandwidths,while projections representing narrower layers of capillaries may bebetter served by relatively smaller and narrow filter sizes. Sincemultiple projection views may be displayed simultaneously, multiple setsof filter parameters may also be used at one time.

Artifacts that result from subject eye motion and other factorsincluding OCT system phase stability and/or positioning errors are acommon source of image degradation in processed OCT angiography results.While either tracking or motion compensation may serve as valuablemethods to reduce or eliminate such motion artifacts, it may also bedesirable to be able to make the most of existing captured data, as thismay result in a simpler scan protocol that ultimately takes less timeand is easier on the imaging subject. It is possible to detectrelatively increased motion on an A-line by A-line basis utilizing meanratio values across A-lines (i.e., no need for a priori segmentation).FIG. 6 illustrates such a method.

According to FIG. 6, for each frame combination, the mean ratio-basedmeasure is calculated for each A-line 600 and then the mean resultsacross A-lines may be smoothed at step 602. The mean ratio-based measure(may be any sort of measure, also including amplitude decorrelation) isintegrated or averaged over the depth of the A-line. If segmentationdata were available, the data could be utilized to limit the integrationor averaging depth. In other embodiments, the calculation in step 600could be, for example, the median or an arbitrary quantile rather thanthe mean. The results over a number of neighboring or nearby A-lines maybe averaged, filtered, or smoothed at step 602 because calculationresults in any one A-line may be subject to a degree of noise andrandomness, and because motion is expected to be highly correlated overa relatively small number of A-lines (for a 100 kHz OCT system, forexample, the time associated with each A-line is just 10 μsec). Forexample, a Gaussian filter can be applied, or a moving average may becalculated across A-lines; however, such a filter or average is notintended to be limiting.

According to the fourth aspect described herein, for each A-line, framecombinations associated with the lowest mean ratios are assumed to matchthe best with one another and are, therefore, deemed to be the leastlikely to have been affected by motion of any sort. The variouscomponent frame combination results can be sorted from lowest (bestmatch) to highest (worst match), and various methods can then be appliedto remove frame combinations from the overall angiographic calculationfor that particular A-line. For example, in one embodiment, an absolutethreshold may be applied, such that any pairs with mean ratios abovesuch threshold are excluded from further use. According to anotherembodiment, a relative threshold—for example, averaging the best andworst results—can be utilized in a similar manner to what is describedabove. In still another embodiment, the top N pairs may be selected,thereby removing a fixed number of pairs representing the worst matches.

In still another embodiment, the list of frame combination results maybe grouped using a technique such as Otsu's method to minimize variancebetween groups. Any entries in the group with the higher motionquantification results may be excluded from the angiographiccalculations. Alternatively, a minimum number of entries in the group tobe included may be specified.

In still another embodiment, the sorted list of results can be traversedone by one from the best to the worst matching results. For each step inthe traversal, the two component frames used in the result calculationare noted. The two component frames of the next-best result (if any) areagain noted, and the process is continued. Once all component framenumbers are encountered at least once, the routine stops and only thoseframe combinations encountered thus far in the traversal are includedwhen averaging the angiographic calculations across the framecombinations. Optionally, the routine may in some cases go back or goforward one or more steps in the traversal process.

It is also noted that one or more of the above methods may also becombined into hybrid methods. For example, an absolute threshold can beapplied, but there also may be a stipulation that at most n entries areincluded (or a minimum of n entries).

Following segmentation at step 408 and/or filtering at step 412, theangiograms or B-scans may be displayed at step 410. Optionally, in step416, the OCT or angiographic data may be rendered, for example, in 3Dfollowing generation of the angiograms at step 406 and/or segmentationof the layer boundaries at step 408. The data may be displayed innumerous manners, including 3D rendering, arbitrary cross-sectionsincluding the X-Z and/or Y-Z plane (cross-section view), the X-Y plane(en-face), and/or any arbitrary combination (i.e., simultaneous views).Planes may also be sliced so as to not be in or orthogonal to thearbitrary X-Z, Y-Z, and/or X-Y planes. These displays may be filteredand/or smoothed; however, this may lower the resolution of the displays.The displays may also be scaled or have a data transform applied tothem. For example, these operations could include taking a logarithmand/or applying a customized grayscale color map.

En-face angiogram projections may also be displayed at step 414following filtering. The displays may include any of thefiltered/smoothed (or unfiltered and unsmoothed) results from thepreviously described processing. The display visualizations may includevasculature within different zones of retinal tissue (in an inner/outersense) such as the superficial retinal arteries and veins, peripapillaryradial network, and the superficial capillary plexus; the deep capillaryplexus; the choriocapillaris, the outer retina; and other disease- orpathology-specific views as appropriate. Furthermore, multipleprojections may be displayed simultaneously, and any such images mayalso be presented simultaneously with the high-resolution OCT orangiography cross-section images, or with the corresponding OCTstructural en-face images. Any combinations of the various imagepermutations are possible within the scope of the present disclosure.The projections may be calculated by taking the maximum intensityprojection (MIP) in each A-line. In other embodiments, the projectionmay be calculated by taking the mean, median, or an arbitrary quantile.The projections may also be calculated by taking the mean of all valuesabove a certain threshold. This threshold may be customizable by theuser of the system.

According to the fifth aspect, no windowing functions or those with lowequivalent noise bandwidth (ENBW) characteristics, and/or spectralreshaping may be utilized. As used herein, the ENBW of a window is thewidth of a rectangle filter with the same peak power gain that wouldaccumulate the same noise power. Assuming a sampling interval T=1, for ageneralized complex window function w(nT), the ENBW is given accordingto:

${ENBW} = \frac{\Sigma_{n}{{w(n)}}^{2}}{{{\Sigma_{n}{w(n)}}}^{2}}$

In some OCT signal processing methods, windowing functions or reshapingof the interferogram data are used to abate discontinuities in thespectral data and to shape the signal waveform, such that when viewed asa periodic signal, is roughly smooth and continuous (e.g., noexcessively high frequencies). This is because such discontinuities andhigh frequencies may result in spectral leakage from a discrete Fouriertransform (DFT). For example, a Hann or equivalent windowing function(to achieve a Gaussian or similar waveform) may be used. However,rectangular windowing functions can yield superior angiographicprojection results, for example, with respect to finer vessel structurestypical in the retina. These finer vessels can appear to be betterconnected in projection images, resulting in an angiographic projectionthat appears to be more realistic and have a higher resolution.

Despite these advantages, by not applying a window or applying arectangular window, then some degree of streaking may appear in the OCTimages. This may lead to a system design tradeoff in which angiographicresults improve at the expense of the clean appearance of the componentOCT images. Thus, OCT structural images can be processed using onewindow function (e.g., a Hann window) while angiographic images can beprocessed using another window function (e.g., a rectangular window orwindow with a lower ENBW). Further, operations such as registration atstep 404 and/or segmentation at step 408 may be based on one or theother of the sets of images. For example, it may be advantageous forsegmentation, even if applied to the angiographic images, to have beencomputed based on a Hann windowing function due to sharper image edgesassociated with less signal leakage. Similarly, in the case ofinter-image registrations, it may be beneficial to register only thesharper set of OCT component images to be utilized with respect to theOCT structural images. Then the determined transform parameters can bereused for angiographic purposes with respect to the blurrier componentframes.

The transfer functions of typical window functions, such as the Hannwindow, have values on the order of about, for example, 50-100 dB down(and often more) away from the center lobe. On the other hand,rectangular windows typically have a transfer function with values onthe order of about, for example, 20 dB. While the use of a windowfunction (or a similarly designed spectral reshaping function) with alower ENBW may have the effect of inducing signal leakage, which mayeffectively cause blurring, it may also effectively reduce thecalculation effects associated with deconstructive speckle. This isbecause such pixels, which might otherwise have very low intensityvalues and, therefore, might be more likely to result in more extremeratio results when paired with corresponding pixels in other frames,will be effectively increased in intensity by a degree that is greaterthan for other pixels of higher intensity. This effectively serves toapply a floor to signal intensities in the OCT images and, in turn, maymoderate computed ratio values. As a result, the angiographiccalculations may be more stable and reliable, and the angiographic imagemay have an improved signal-to-noise ratio. A comparison of the resultsof an example swept source based angiogram utilizing a rectangularwindow and a Hann window are illustrated in FIG. 7. As can be seen, theprocessing with the rectangular window leads to reduced noise (e.g. inand surrounding the foveal avascular zone), apparently higherangiographic signal-to-noise ratio/fidelity, and better overallconnectedness of the inner retinal (superficial) vasculature.

While the rectangular window was described in the above examples, it isnoted that other window functions, including those not traditionallythought of as high-resolution OCT windows, may be used. For example, aTukey window with a low alpha (such as 0.1 or less) may be used. Tukeywindows have a relative advantage when compared to rectangular windowsin that a possible discontinuity in the spectrum is abated and,therefore, effects to the OCT images themselves (e.g., streaking) may bereduced. Still, windowing functions that have an ENBW that is notablyless than that of the Hann window can be expected to perform insubstantially the same manner as the rectangular window. For example, anENBW less than about 1.23 can yield superior angiographic projectionresults. It is also noted that the spectrum may be shaped by either orboth optical and/or numerical methods, and the lower ENBW characteristicdiscussed above may be applied thereto.

While the above description relates to particular windowing functions,these functions are not intended to limit the scope of the presentdisclosure. Still further, the windowing functions may be implemented aseither hardware or software, and the ENBW criteria can be applied. Forexample, criteria such as the ENBW may be applied to the envelope of theinterferogram as it is immediately before a discrete Fourier transform.However, the present disclosure should not be limited to this timing.

With respect to the sixth aspect described herein, OCT images forangiography may be computed using a partial spectrum that represents asubset of the full spectral data. This may be desirable in somescenarios, such as when spectral reshaping is utilized. This may yieldimproved results as spectral reshaping may effectively amplify thesignal-to-noise ratio over some portions of the spectrum.

With respect to a seventh aspect described herein, a minimum intensitythreshold can be applied within the general calculation methodology todetermine over which pixels to calculate a ratio-based or geometricstandard deviation result. According to this aspect, when the signalintensity of a particular pixel location is at or above the minimumintensity, the value (e.g. ratio value) is calculated. Otherwise, theangiographic output is set to zero (or any arbitrary value).

The minimum intensity threshold can be calculated relative to weakforeground signal (e.g., relatively hyporeflective retinal signal in thecase of retinal angiography). In contrast to a minimum intensitythreshold based on calculations relative to a measured background noise(e.g., when a sample beam is blocked from detection or in portions of animage that do not correspond to any sample or that have scatteringproperties to which the system lacks sensitivity), the threshold basedon a weak foreground signal can yield a better signal-to-noise ratio inthe resulting angiographic image and greater continuity of the imagedvasculature. The foreground-based threshold also allows a consistentlyhigh quality result to be delivered via a default parameter set. Inother words, consistent angiography results can be achieved acrossvarious machines with differing noise characteristics. Nevertheless, thebackground-based threshold may still be used without departing from thescope of the present disclosure.

FIG. 8 illustrates a flow chart for determining the minimum intensitythreshold using a weak foreground signal. According to one embodiment,an OCT image obtained at step 800, which can include ocular tissue, maybe segmented at step 802 in any manner. For example, accurate layerboundaries may be determined in order to delineate the retina, choroid,and/or any desired layer. Alternatively, a moving window function offixed or variable size may be used within each A-line to determine theforeground region by maximizing integrated signal content. Furthermore,the image(s) may be the same as that (those) being used to generateangiographic results, or they can be an entirely different image or setof images. This process could also be performed beforehand based on arepresentative image or set of images with the results stored as acalibration parameter or parameters.

Next, a histogram based on the segmented foreground data is optionallygenerated at step 804. This foreground data may correspond to the fullretina and/or choroid. Alternatively, the foreground data mayspecifically correspond to a relatively hyporeflective layer or set oflayers that might include the ganglion cell layer (GCL), inner nuclearlayer (INL), or the outer nuclear layer (ONL). Then, using either thehistogram or a sorted list of pixel intensities, a value is extracted atstep 806 according to a predetermined percentile or quantile. Forexample, the full retina (which may include some choroid) is utilized tofind the pixel intensity that falls at approximately the 25-30%percentile (a relatively low threshold) when ordered from low to high.If a hyporeflective layer or group of layers were utilized in the priorstep, then a higher percentile could be used (e.g., between 50% (median)and 75%) with data ordered low to high. It is noted that any percentilelevel or pixel intensity may be used within the scope of the presentdisclosure based on desired results. The pixel intensity value at thispoint then serves as the minimum intensity threshold. The minimumintensity threshold can be automatically determined based on a fixedparameter (e.g., a prespecified percentile or quantile). In someembodiments, the parameter can be user-definable.

It is noted that the minimum intensity threshold may be based on thepixel intensity in any arbitrary image, including any of the individualframes or the averaged image. Additionally, different frame combinationscould utilize a different image or images as the basis for determining athreshold.

FIG. 9A illustrates a comparison between the SSADA method and atechnique described herein. In FIG. 9, the same data set is calculatedusing a technique described herein and a method approximating SSADAprocessing. Both images are based on maximum intensity projection overidentical depths and utilize the same normalization methodology in theirdisplays. It can be seen that the image generated by the above-describedtechnique provides greater angiographic signal intensity and detail, forexample in and around the optic nerve head, resulting in an image withmore consistent appearance. Similarly, FIG. 9B illustrates a comparisonof choroidal neovascular membrane images between standard deviationinterframe calculations and techniques described herein. Again, theimage generated by the above-described technique provides greaterangiographic signal intensity and detail, as well as greater consistencyacross the imaging area.

FIG. 10 further illustrates a comparison between amplitude decorrelationmethods and those described herein by plotting the relative sensitivityadvantage of a ratio-based approach over amplitude decorrelation. As canbe seen, for lower flows (those having a low one minus pixel intensityratio), ratio-based method (OCTARA Ratio Analysis) provides a greaterangiographic result. Accordingly, images formed through a ratio-basedanalysis are more sensitive (clearer distinction) to vasculature withlower blood flows. For example, based on the plot of FIG. 10, theratio-based method is about as sensitive to a 0.1 on minus pixelintensity ratio, as amplitude decorrelation is for a 0.4 one minus pixelintensity ratio. Furthermore, similar to the tabular data presentedabove, given the curvature of the two plot lines it can be observed thatthe ratio-based analysis demonstrates greater sensitivity to lower bloodflows relative to the flow at greater, intermediate levels as well. Theratio-based result, therefore, is associated with both greater linearityas well as higher dynamic range.

It is also noted that parameters of the OCT system used for imaging canhave an effect on the resultant images. That is, for example, OCTangiography can require repeated scanning of the same position in theeye and, therefore, higher OCT imaging rates can benefit OCT angiographyto acquire densely sampled data sets. However, OCT imaging sensitivityscales inversely with speed and is limited by the maximum permissibleexposure (MPE) values of standards such as ANSI Z136.1, ISO 15004-2 orIEC 60825-1. The maximum achievable sensitivity of a high speed(Fourier-domain) OCT in the case of a perfect reflector and losslessoptical system is given as:

${Sensitivity} = {10\mspace{14mu}{\log_{10}( \frac{\rho\; P_{MPE}}{2{ef}_{A}} )}}$where ρ is the photodetector responsivity, P_(MPE) is the MPE opticalpower on the eye, e is the charge of an electron, and f_(A) the OCTimaging speed.

One feature of OCT angiography is its ability to detect blood flow indifferent layers of the retina. Both the motion contrast calculationsand retinal layer segmentation rely on sufficient sensitivity in OCTimaging to enable enface visualization of each layer of vascularnetworks in the retina and choroid. With lower sensitivity, the highernoise not only detrimentally affects motion contrast calculations, butalso can make it difficult to perform segmentation for visualizingvasculature within specific layers of the retina. Therefore, manyclinical OCT devices require sensitivity above 95 dB. With a 1mmdiameter beam incident on the cornea, the MPE is limited to 0.79 mWaccording to ISO 15004-2. Assuming a typical photodetector responsivityof 0.7 A/W, the maximum OCT imaging speed is less than 485 kHz tomaintain a reasonable sensitivity according to the expression above.

A higher MPE can be allowed with a larger diameter beam incident on thecornea. However, a larger beam can decrease the robustness of the deviceby having smaller margins for misalignment through the pupil and shorteraxial field of view at the beam focus. Even with an increased MPE,maximum OCT imaging speed suitable for clinical imaging is likely below1 MHz given current safety standards. Averaging multiple OCT images canenhance image quality in high speed OCT, but it does not necessarilyhelp OCT angiography motion contrast calculations. In light of theabove, the OCT imaging speed for OCT angiography may be an A-scan rateof less than 1 MHz, for example several hundreds of kHz. For example,some OCT implementations may have an A-scan rate of 25 kHz-800 kHz.There are no such lower “boundaries” or “limits” other thanconsiderations such as those relating to artifacts/noise from eye motionof the subject and desired scan density. Nevertheless, the aspectsdescribed herein may be used with any OCT system, or applied to dataobtained with other imaging modalities.

While this disclosure is based on the OCT imaging modality, it is notlimited to OCT. For example, it is applicable to ultrasound as well. Itshould also be noted that while a technique described herein is relatedto angiography and retinal vessel visualization, the techniques are notlimited in this manner either; but rather, may be applied to othervisualizations involving fluid or object flow, or other moving volumes.Flow or motion in the vitreous is one example.

It is to be noted that any of the aspects or combination of aspectsdescribed above may be implemented via hardware or software. Whensoftware, the computer program including instructions for causing acomputer to execute at least a portion of the above-described aspects isstored on a non-transitory computer-readable medium. When executed thesoftware causes a computer, including for example a processor(s), toexecute the instructions stored thereon. These aspects may beimplemented on a processor or a plurality of processors, such as agraphics processing unit (GPU) or similar dedicated graphics processor.These processor(s) also may be embedded or integrated with otherprocessors designed for a separate purpose, for example, as part of acentral processing unit (CPU). Such processor(s) may also be forgeneral-purpose computing on a graphics processor unit (GPGPU). A“processor” as used herein refers to any, or part of any, electricalcircuit comprised of any number of electrical components, including, forexample, resistors, transistors, capacitors, inductors, and the like.The circuit may be of any form, including, for example, an integratedcircuit, a set of integrated circuits, a microcontroller, amicroprocessor, a collection of discrete electronic components on aprinted circuit board (PCB) or the like. The processor may also standalone or be part of a computer used for operations other than processingimage data. Implementation of these aspects by hardware or software maybe realized in any number of electronic devices and/or applications,including but not limited to, personal computers, servers, integratedOCT or similar imaging machines, and the like. Moreover, the aboveaspects and/or combination of aspects may be stored in memory which isexecutable by one of said processors. It should also be noted that theabove description is non-limiting, and the examples are but only a fewof many possible processors and implementations envisioned.

While various features are presented above, it should be understood thatthe features may be used singly or in any combination thereof. Further,it should be understood that variations and modifications may occur tothose skilled in the art to which the claimed examples pertain. Theexamples described herein are exemplary. The disclosure may enable thoseskilled in the art to make and use alternative designs havingalternative elements that likewise correspond to the elements recited inthe claims. The intended scope may thus include other examples that donot differ or that insubstantially differ from the literal language ofthe claims. The scope of the disclosure is accordingly defined as setforth in the appended claims.

What is claimed is:
 1. An angiographic optical coherence tomography(OCT) method comprising: calculating values of OCT images of a volume,the OCT images being B-scan frames repeatedly captured from a samelocation of the volume; generating an angiographic image based on thecalculated values; and displaying, rendering, and/or storing theangiographic image, wherein the values are calculated by comparingrespective pixels of a permutation of interframe combinations of the OCTimages, wherein the permutation of interframe combinations comprises: afirst interframe combination having frames separated by a first numberof frames, and a second interframe combination having frames separatedby a second number of frames, the second number of frames beingdifferent than the first number of frames.
 2. The method of claim 1,wherein a contrast of each pixel of the angiographic image correspondsto a different one of the calculated values.
 3. The method of claim 1,wherein: the calculated values represent a dissimilarity between thecorresponding pixels, and a sensitivity of the calculated values to thedissimilarity is greater than a sensitivity of values determinedaccording to an amplitude decorrelation method.
 4. The method of claim1, further comprising: averaging the calculated values for an X-Yposition of the OCT images for which the values are calculated.
 5. Themethod of claim 4, further comprising: comparing the averaged value to acriterion; and excluding the averaged value when the averaged value doesnot meet the criterion.
 6. The method of claim 5, wherein the averaging,comparing, and excluding are performed A-line by A-line.
 7. The methodof claim 1, wherein at least one of the OCT images is captured byillumination with a partial spectrum of an OCT light source.
 8. Themethod of claim 1, wherein the values are only calculated forcorresponding pixels of the OCT images having an intensity greater thana minimum pixel intensity threshold.
 9. The method of claim 8, whereinthe minimum pixel intensity threshold is a pixel intensity at apredetermined percentile of pixel intensities according to a histogramor sorted list of pixels of at least a portion of the OCT images. 10.The method of claim 1, wherein A-scans of the OCT images are captured ata rate less than 1 MHz.
 11. The method of claim 1, wherein A-scans ofthe OCT images are captured at a rate between 25 kHz and 800 kHz. 12.The method of claim 1, wherein the permutation of interframecombinations of the OCT images is predetermined.
 13. The method of claim1, wherein the permutation of interframe combinations of the OCT imagescomprises at least one combination of OCT images separated by more thanone frame.
 14. The method of claim 1, wherein the permutation ofinterframe combinations of the OCT images comprises at least twocombinations of OCT images having different time separations.
 15. Anangiographic optical coherence tomography (OCT) method, comprising:calculating values of OCT images of a volume, the OCT images beingB-scan frames repeatedly captured from a same location of the volume;generating an angiographic image based on the calculated values; anddisplaying, rendering, and/or storing the angiographic image, whereinthe values are calculated by comparing respective pixels of apermutation of interframe combinations of the OCT images, and wherein anequivalent noise bandwidth (ENBW) for the OCT images is greater than theENBW for the angiographic image.
 16. An angiographic optical coherencetomography (OCT) method comprising: calculating values of a first OCTimage, a second OCT image, and a third OCT image, the first, second, andthird OCT images being B-scan frames repeatedly captured from a samelocation; generating an angiographic image based on the calculatedvalues; and displaying, rendering, and/or storing the angiographicimage, wherein the values are calculated by comparing respective pixelsof the first and second OCT images, comparing respective pixels of thesecond and third OCT images, and comparing respective pixels of thefirst and third OCT images, and wherein the second OCT image is capturedafter the first OCT image, and the third OCT image is captured after thesecond OCT image.